IPN60090

1853164-83-6

532.52

DMSO : 60 mg/mL (ultrasonic)

Metabolic Enzyme/Protease

IPN-60090 is an orally active and highly selective inhibitor of glutaminase 1?(GLS1; IC50=31 nM), with no activity observed against GLS-2. IPN-60090 exhibits excellent physicochemical and pharmacokinetic properties in vivo. IPN-60090 can be used for solid tumors research, such as lung and ovarian cancers.
IC50 & Target: IC50: 31 nM (GLS1)
In Vitro: There are two known isoforms of glutaminase: GLS-1 (also called kidney-type or KGA), and GLS-2 (also called liver-type or LGA). GLS-1 is ubiquitous and GLS-2 expression appears limited primarily to the liver.
In a dual-coupled enzyme assay, IPN60090 inhibits purified recombinant human GLS-1 (GAC isoform) with an IC50 of 31 nM, and has no activity against GLS-2, with an IC50 of >50000 nM.
IPN60090 inhibits the proliferation of A549 cells with an IC50 of 26 nM.

In Vivo: IPN60090 (3 mg/kg for i.v.; 10 mg/kg for p.o.) has excellent pharmacokinetic properties, with CL=4.1 mL/min/kg, t1/2=1 hour, Cmax=19 uM, F%=89%.
IPN-60090 (oral administration; 100 mg/kg; twice daily; 30 days) shows similar efficacy and target engagement to CB-839 (HY-12248) dosed orally at 250 mg/kg twice daily. And the 100 mg/kg BID dose of IPN-60090 is a tolerated dose for the following model study.
IPN-60090 (oral administration; 100 mg/kg; twice daily; 30 days; monotherapy or in combination with TAK228 (HY-13328)) causes tumor growth inhibition. IPN-60090 alone demonstrates robust in vivo target engagement in a dose-dependent manner. The glutamate/glutamine ratios and the free plasma concentrations of IPN-60090 at 4 hours post-dose on both day 4 and day 28 are all decreased. Furthermore, IPN-60090 in combination with TAK228 strongly causes an 85% tumor growth inhibition, IPN-60090 alone causes a 28% tumor growth inhibition in vivo.